Bronchogenic carcinoma is the leading cause of cancer deaths in man. Both epidelogic and experimental studies have suggested the importance of asbestos and other minerals as cofactors in the development of this lesion. This project is designed to test the hypothesis that asbestos and selected non-asbestos fibers and particulates (i.e. crocidolite and chrysotile asbestos, attapulgite, kaolin and hematite) serve as tumor promoters in carcinogenesis of the respiratory tract. Using hamster tracheal grafts exposed sequentially to low dosages of benzo(a)-pyrene (BP) and test minerals, we will determine whether numbers of tracheal neoplasms are increased above numbers developing with use of BP alone. In additional studies, we will explore the interactions of minerals with hamster tracheal organ cultures and cloned, normal epithelial cell lines. Specifically, we will address the questions: Do minerals cause increased uptake of (3H)- thymidine, an indicator of DNA synthesis? Do minerals induce squamous metaplasia (i.e. alteration in differentiation) of the normal mucociliary epithelium? Do minerals stimulate the activity of ornithine decarboxylase and release of oxygen free radicals from epithelial cells? and Do minerals interact with specific receptors as does epidermal growth factor (EGF) with tracheal epithelial cells? The importance of mineral shape and size in eliciting these responses will be determined. Elucidation of the mechanisms of action of minerals which are important in tumor promotion is intrinsic to understanding the process of two-stage carcinogenesis. The intended emphasis is on properties which minerals might have in common with phorbol esters, the classical tumor promoters in mouse skin.